The main goal of this proposal is to elucidate possible mechanisms through which cholesterol ester would accumulate in atherosclerotic lesions in the arterial wall. The specific aim of this research program is to determine whether the type of lipid fed in the diet will alter serum lipoproteins sufficiently to affect their interaction with smooth muscle cells and macrophages, thus altering their cholesterol metabolism. The two diets were chosen in view of the fact that a coconut oil and cholesterol diet produce lipid-rich lesions while a peanut oil and cholesterol diet produce lesions which are more cellular with abundant collagen and less lipid. In addition, the lipoprotein composition and concentration induced by these diets are quite different. The areas of proposed research are: (a) A determination of the interaction of iodinated normal and diet-altered lipoproteins with specific or nonspecific cell surface receptors on smooth muscle cells and macrophages. Binding, uptake and degradation of LDL, VLDL and HDL will be examined. (b) Effect of changes of concentration of one lipoprotein, HDL in particular, with respect to the cell-lipoprotein interactions of other lipoproteins. (c) Alterations in cellular cholesterol metabolism upon exposure to the abnormal lipoproteins with particular emphasis on cholesterol ester accumulation and cholesterol efflux. The methods used will include cell culture, gas-liquid chromatography, lipid biochemistry and iodination of lipoproteins.